A5026863845- Cancer Treatment and Pharmacology
- Pharmacogenetics and Drug Metabolism
- Lung Cancer Treatments and Mutations
- Computational Drug Discovery Methods
- Cancer therapeutics and mechanisms
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Glioma Diagnosis and Treatment
- Statistical Methods in Clinical Trials
- HER2/EGFR in Cancer Research
- Medical Imaging Techniques and Applications
- HIV/AIDS drug development and treatment
- Advanced Breast Cancer Therapies
- Cancer, Hypoxia, and Metabolism
- Protein Degradation and Inhibitors
- Biosimilars and Bioanalytical Methods
- Drug Transport and Resistance Mechanisms
- Acute Lymphoblastic Leukemia research
- Biochemical and Molecular Research
- Brain Metastases and Treatment
- Radiopharmaceutical Chemistry and Applications
- Hepatocellular Carcinoma Treatment and Prognosis
- Pharmaceutical studies and practices
- Neutropenia and Cancer Infections
- Epigenetics and DNA Methylation
National Institutes of Health
2008-2025
National Cancer Institute
2014-2023
Center for Cancer Research
2005-2023
Frederick National Laboratory for Cancer Research
2013-2022
NeuroDevelopment Center
2019
Seagen (Canada)
2017
Novartis (Switzerland)
2017
Huntsville Hospital
2017
Takeda (France)
2017
WinnMed
2017
Background: Many cancer patients in phase I clinical trials are treated at doses of chemotherapeutic agents that below the biologically active level, thus reducing their chances for therapeutic benefit. Current often take a long time to complete and provide little information about interpatient variability or cumulative toxicity. Purpose: Our objective was develop alternative designs so fewer subtherapeutic dose levels, reduced duration, important (i.e., toxicity maximum tolerated dose)...
Regional drug delivery is an approach designed to improve the selectivity of chemotherapy. When compared with systemic administration, regional can potentially increase concentrations at tumor sites and/or lower exposure. Pharmacokinetic analysis evaluate or even predict relative advantage delivery. Based on a quantitative delivery, some drugs and are more favorable than others. The formulas for therapeutic intraarterial, intrathecal, intraperitoneal have similar structure. ratio total body...
We investigated the clinical pharmacokinetics of azidothymidine (N3TdR) as part a phase I/II trial in treatment acquired immunodeficiency syndrome and related diseases. During 6-week course therapy, drug levels plasma, cerebrospinal fluid, urine were determined by HLPC. The plasma half-life N3TdR was 1.1 hour. total body clearance 1.3 L/kg/hr. At intravenous doses 5 mg/kg or oral 10 mg/kg, continuously maintained above target level 1 μmol/L. Oral bioavailability 63% ± 13%. Substantial...
Purpose We conducted the first phase 0 clinical trial in oncology of a therapeutic agent under Exploratory Investigational New Drug Guidance US Food and Administration. It was first-in-human study poly (ADP-ribose) polymerase (PARP) inhibitor ABT-888 patients with advanced malignancies. Patients Methods administered as single oral dose 10, 25, or 50 mg to determine range time course over which inhibits PARP activity tumor samples peripheral blood mononuclear cells, evaluate pharmacokinetics....
Abstract To date, over 100 small-molecule oncology drugs have been approved by the FDA. Because of inherent heterogeneity tumors, these small molecules are often administered in combination to prevent emergence resistant cell subpopulations. Therefore, new strategies overcome drug resistance patients with advanced cancer needed. In this study, we performed a systematic evaluation therapeutic activity 5,000 pairs FDA-approved against panel 60 well-characterized human tumor lines (NCI-60)...
Wee1 tyrosine kinase phosphorylates and inactivates cyclin-dependent (Cdk) 1/2 in response to DNA damage. AZD1775 is a first-in-class inhibitor of with single-agent antitumor activity preclinical models. We conducted phase I study adult patients refractory solid tumors determine its maximum-tolerated dose (MTD), pharmacokinetics, modulation phosphorylated Tyr15-Cdk (pY15-Cdk) histone H2AX (γH2AX) levels paired tumor biopsies.
Abstract Since the early 1990s Developmental Therapeutics Program of National Cancer Institute (NCI) has utilized a panel 60 human tumor cell lines (NCI60) representing 9 tissue types to screen for potential new anticancer agents. To date, about 100,000 compounds and 50,000 natural product extracts have been screened. Early in this program it was discovered that pattern growth inhibition these similar mechanism. The development COMPARE algorithm provided means by which investigators,...
In this phase II trial, 105 eligible patients with no prior chemotherapy and advanced sarcoma received doxorubicin, ifosfamide, dacarbazine (DTIC) mesna uroprotection (MAID). Starting doses of these drugs were 60, 7,500, 900 mg/m2 divided over 72 hours by continuous infusion, respectively. Mesna was given for 84 to 96 at 2,500 mg/m2/d. Myelosuppression dose limiting, causing the only toxic death (sepsis). Nonhematologic toxicity consisted predominantly anorexia vomiting. Severe mucositis,...
Induction therapy is now successful in producing a complete remission more than 90 per cent of patients with acute lymphoblastic leukemia.1 , 2 However, maintenance remains major problem, since third standard risk and approximately 80 high relapse despite periodic intensification chemotherapy continual chemotherapy.3 The daily administration oral mercaptopurine forms the backbone for leukemia; most treatment regimens also include weekly or biweekly methotrexate. rationale giving orally has...
Clinical Pharmacology and Therapeutics (1992) 51, 465–473; doi:10.1038/clpt.1992.47
A two-compartment physiologic pharmacokinetic model has been developed for 5-fluorouracil (5FU). This model, which incorporates saturable whole body clearance, satisfactorily predicts disappearance kinetics after an intravenous bolus and steady-state levels during constant infusions. half-saturating concentration (KM) of 15 microM was determined by comparison simulations with literature data. Both hepatic extrahepatic elimination can be inferred 5FU, but the exact anatomic or compartmental...
Earlier studies suggested that the dose of 6-mercaptopurine (6-MP) can be reduced substantially when drug is given with allopurinol. We studied effect allopurinol on kinetics oral and intravenous 6-MP. Studies conducted initially in rhesus monkeys subsequently man 6-MP doses 100 mg/m2 75 mg/m2, demonstrated pretreatment resulted a nearly 400% increase peak plasma concentration (from mean 0.54 microM to 2.1 microM) 500% (0.74 3.7 microM). Allopurinol also led 300% AUC after 121 microM/min 391...